Evaluation of longitudinal changes in choroidal thickness during pregnancy and postpartum using widefield swept-source optical coherence tomography

Abstract

In this exploratory study, we investigated longitudinal changes in whole, luminal, and stromal choroidal thickness (CT) during pregnancy and the postpartum period using widefield swept-source optical coherence tomography. Ten eyes of five healthy pregnant women were examined monthly from mid-pregnancy to delivery and, when possible, at least 1 year postpartum. CT was measured over a 20 × 23 mm area centered on the fovea and was analyzed using a grid of three concentric subfields defined by circles measuring 3, 9, and 18 mm in diameter. At 5 months’ gestation, the mean central CT was 258 ± 35 μm. For the right eye, the mean CT within the entire 18-mm circle showed a nonsignificant increase between 4 and 5 months of gestation (P = 0.078), followed by a significant decrease between 5 and 9 months (P = 0.038). After delivery, the choroid became thicker again, although this change was not statistically significant (P = 0.117). All subfields showed similar fluctuations. Thickness recovered partially postpartum, mainly reflecting changes in the luminal rather than in the stromal component. These findings suggest that pregnancy induces dynamic, reversible vascular changes in the choroid, which may reflect ocular adaptations to systemic circulatory alterations.

Supplementary Information

The online version contains supplementary material available at 10.1038/s41598-025-33485-7.

Introduction

Pregnancy induces profound hormonal, hemodynamic, and metabolic changes, including increased circulating levels of estrogen, progesterone, and cortisol, expansion of plasma volume, increased cardiac output, and decreased systemic vascular resistance^1–5. Although these systemic adaptations are essential for maintaining maternal–fetal circulation, they can secondarily influence ocular physiology, particularly within the choroid, a highly vascularized ocular tissue. Clinically, pregnancy has been associated with ocular complications such as central serous chorioretinopathy (CSC) and hypertensive choroidopathy^6,7.

However, the results of reports describing pregnancy-associated changes in choroidal thickness (CT) have been inconsistent. Some cross-sectional studies found no significant difference in subfoveal CT between pregnant and nonpregnant women^8,9, whereas others demonstrated increased thickness in pregnant women^10–12. These discrepancies may reflect both interindividual variability due to factors such as age and axial length^13–15 and insufficient capture of dynamic fluctuations across gestation. Moreover, most prior studies have been limited to subfoveal measurements. Recent advances in widefield swept-source optical coherence tomography (SS-OCT) have highlighted the importance of assessing choroidal alterations in not only the macula but also the periphery^16–20. Furthermore, separating luminal and stromal components enables a more detailed interpretation of choroidal alterations, particularly those related to vascular modulation^21–25.

The aim of this study was to provide a comprehensive characterization of pregnancy-related choroidal changes through longitudinal investigations of whole, luminal, and stromal CT changes in both the macular and peripheral regions during pregnancy and the postpartum period using widefield SS-OCT.

Methods

Participants

This observational, exploratory study was approved by the Institutional Review Board of Kyoto University Graduate School of Medicine and adhered to the tenets of the Declaration of Helsinki. Written informed consent was obtained from all participants before enrollment.

We included 10 eyes of five consecutive healthy pregnant women without ocular or systemic disease before pregnancy who consented to undergo monthly examinations at the Department of Ophthalmology, Kyoto University Hospital. All participants underwent comprehensive ophthalmic evaluations, including measurements of refraction, decimal best-corrected visual acuity (BCVA) with a 5-m Landolt chart, and axial length (AL). Objective refraction was assessed using an autorefractor (ARK-530 A; NIDEK, Gamagori, Japan), and AL was measured using an optical biometer (IOLMaster 700; Carl Zeiss Meditec, Dublin, CA, USA).

Widefield SS-OCT imaging

After resolution of severe morning sickness, each participant underwent monthly widefield swept-source OCT (SS-OCT) examinations until late pregnancy, with additional follow-up performed at ≥ 1 year postpartum when feasible. All scans were obtained at a fixed time of day for each participant.

All OCT datasets were acquired using an SS-OCT system (Xephilio OCT-S1; Canon Inc., Tokyo, Japan) operating at a central wavelength of 1010–1110 nm and a scanning speed of 100,000 A-scans/s. The focusing spot was set at 30 μm to achieve widefield coverage without additional hardware. Three-dimensional volume data were acquired over a 20-mm (vertical; 128 B-scans) × 23-mm (horizontal; 1024 pixels) × 5.3-mm (depth; 1396 pixels) region in enhanced depth imaging mode. The system’s built-in averaging and noise-reduction algorithms were automatically applied. The choroid was defined as the layer between Bruch’s membrane and the chorioscleral interface. Automated segmentation was performed using the built-in artificial intelligence-based software. All B-scans were reviewed by two independent retina specialists (TK and NN). Manual correction was performed when segmentation errors were observed, and discrepancies were resolved by a senior reviewer (YM). OCT images were analyzed in batches, and graders were blinded to the month of gestation to reduce potential bias.

CT maps were generated using a previously validated automated method (Fig. 1)^14,16,26. A grid of concentric circles with diameters of 3, 9, and 18 mm was centered on the fovea. The inner and outer rings were defined as the subfields between the 3- and 9-mm circles and the 9- and 18-mm circles, respectively. CT values were corrected for AL-related magnification using the modified Littmann formula (Bennett procedure)^16,27.

Fig. 1.

Choroidal thickness (CT) evaluations using enhanced-depth imaging widefield swept-source optical coherence tomography. Three-dimensional volume data are obtained over a 20-mm (vertical; 128 B-scans) × 23-mm (horizontal; 1024 pixels) × 5.3-mm (depth; 1396 pixels) area in enhanced-depth imaging mode. (A) A B-scan image. (B) The choroid is defined as the tissue between Bruch’s membrane and the chorioscleral interface, with accurate automated segmentation of the inner and outer borders. (C) Corresponding CT map. (D) Measurement grid comprising three concentric circles (diameters: 3 mm, 9 mm, and 18 mm) centered on the fovea. The inner and outer rings are defined as the subfields between the 3- and 9-mm circles and the 9- and 18-mm circles, respectively. Mean CT values (µm) are calculated for each subfield.

Luminal and stromal thicknesses

Luminal and stromal components were quantified using a validated binarization method (Fig. 2)^21–25. Each B-scan was processed with ImageJ software (version 1.51; National Institutes of Health, Bethesda, MD, USA). Gaussian filtering was applied for noise reduction²⁸, followed by binarization with the Niblack Auto Local Threshold algorithm²⁵.

Fig. 2.

Luminal and stromal choroidal thickness evaluations. (A) A B-scan image. (B) After Gaussian filtering for noise reduction, the Niblack Auto Local Threshold algorithm has been applied to segment the choroid into luminal (blue) and stromal (orange) regions. The thickness of each component is measured and reconstructed into three-dimensional maps. (C,D) Luminal (C) and stromal (D) thickness maps. Each map is evaluated using the same grid applied for whole choroidal thickness measurements.

The binarized images were separated into luminal and stromal regions. The thickness of each component was measured on every A-scan and reconstructed into three-dimensional thickness maps. The same grid used for CT measurements was applied to obtain mean luminal and stromal thickness values for each subfield.

Except for the verification of segmentation, the measurement process was fully automated using the built-in macro system of ImageJ software. Manual correction was required only infrequently, and all corrections were made following predefined criteria.

Statistical analysis

All analyses were conducted with JMP Pro version 18.0 (SAS Institute Inc., Cary, NC, USA). Continuous variables are presented as mean ± standard deviation (SD). BCVA values were converted to logarithm of the minimum angle of resolution units. For inferential statistical analyses, one eye per participant (right eye) was used to maintain independence of observations, although measurements were collected for both eyes and are presented as descriptive statistics. Paired t-tests were applied for comparisons between timepoints, with significance defined as P < 0.05. For each analysis, only data available at each timepoint were included, and missing values were handled by listwise exclusion without imputation.

Results

This study analyzed 10 eyes of five pregnant women (mean age, 35.0 ± 2.6 years; Table 1). Two participants were primiparous and three were multiparous; none had multiple gestations. One developed gestational diabetes; no other complications were recorded for the others. Four participants were evaluable from 4 months of gestation, while one with prolonged morning sickness was included from 5 months. Because of placenta previa requiring bed rest or delivery, two participants were followed until 8 months, while the remaining three were followed until 9 months. At ≥ 1 year postpartum, three participants were reassessed, whereas one had conceived again and another was lost to follow-up. For comparisons between timepoints, 5-month values (available for all cases) were used as reference values, with subsequent values expressed relative to this baseline (Supplemental Fig. 1). At 5 months, the mean CT was 258 ± 35 μm in the central 3-mm circle, 255 ± 30 μm in the inner ring, and 210 ± 16 μm in the outer ring.

Table 1.

Characteristics of healthy pregnant women who underwent evaluations of choroidal thickness changes during pregnancy and postpartum.

Parity, primiparous/multiparous, n	2/3
Singleton/multiple pregnancy, n	5/0
Mean age, years (range, years)	35.0 ± 2.6 (31–38)
BCVA in logMAR (range, Snellen equivalent)	−0.12 ± 0.07 (20/20–20/13)
Pregnancy-related complications
Gestational diabetes, n	1
Gestational hypertension, n	0
Ocular complications, n	0

Data are presented as mean ± standard deviation, unless otherwise indicated.

BCVA, best-corrected visual acuity; logMAR, logarithm of the minimum angle of resolution.

Whole choroidal thickness

For the right eye, the mean CT within the entire 18-mm circle showed a nonsignificant increase between 4 (95% confidence interval [CI]: 93.8–100.6%) and 5 months (100%) of gestation (P = 0.078), followed by a significant decrease between 5 and 9 (95% CI: 81.6–98.6%) months (P = 0.038). After delivery (95% CI: 95.5–99.2%), the choroid became thicker again, although this change was not statistically significant (P = 0.117). Longitudinal changes in CT across subfields for both eyes are summarized in Fig. 3. Despite the small sample size, all subfields demonstrated a consistent pattern: CT increased from 4 to 5 months, decreased markedly between 5 and 6 months, stabilized from 6 to 7 months, and then gradually decreased toward late pregnancy (Fig. 4). At ≥ 1 year postpartum, CT values for every subfield were consistently higher than those at 9 months of gestation, indicating a modest postpartum increase.

Fig. 3.

Longitudinal changes in choroidal thickness (CT) during pregnancy and postpartum. Graphs showing changes in CT across different subfields: (A) Central 3-mm circle, (B) inner ring, (C) outer ring. Despite the small sample size, consistent patterns are observed across all subfields: CT increases between 4 and 5 months, decreases markedly from 5 to 6 months, stabilizes between 6 and 7 months, and gradually decreases thereafter toward late pregnancy. At ≥ 1 year postpartum, CT values are consistently greater than those at 9 months, showing partial recovery.

Fig. 4.

Representative case of longitudinal choroidal changes during pregnancy.

The images show subtraction maps illustrating monthly changes in choroidal thickness (CT) for both eyes of a 31-year-old pregnant woman ((A–F) right eye, (G–L) left eye), generated using the Canon Research Tool (Canon Inc., Tokyo, Japan). Areas of relative thickening are shown in yellow to red, while areas of thinning are shown in light blue to dark blue. Consistent temporal patterns are observed: CT increases between 4 and 5 months (A,G), decreases markedly from 5 to 6 months (B,H), remains relatively stable between 6 and 7 months (C,I), and gradually decreases thereafter toward late pregnancy (D,E,J,K). At ≥ 1 year postpartum, the choroid shows a subsequent increase in thickness (F,L).

Luminal and stromal thicknesses

When analyzed separately, luminal and stromal components showed distinct patterns (Fig. 5). Luminal thickness changes were closely parallel to whole CT changes, with an increase from 4 to 5 months, a decrease from 5 to 6 months, relative stability from 6 to 7 months, and a further decline beyond 7 months. At ≥ 1 year postpartum, luminal thickness values were higher than those at 9 months. These findings indicated that the dynamic changes observed during pregnancy and the postpartum increase were primarily driven by the luminal component. In contrast, stromal thickness showed modest fluctuations, remaining largely stable with only minor late-pregnancy decreases.

Fig. 5.

Longitudinal changes in luminal and stromal choroidal thicknesses during pregnancy and the postpartum period. Graphs showing changes in luminal and stromal thicknesses across different subfields:

(A) central 3-mm circle, (B) inner ring, (C) outer ring. Luminal thickness changes are closely parallel to whole choroidal thickness changes, showing an increase from 4 to 5 months, a decrease from 5 to 6 months, relative stability from 6 to 7 months, and a further decline beyond 7 months, with partial recovery postpartum. In contrast, stromal thickness exhibits only modest fluctuations and remains relatively stable throughout pregnancy, with minor late-pregnancy decreases.

Discussion

In this study, we longitudinally evaluated choroidal changes during pregnancy, analyzing both macular and peripheral regions.

The results of previous reports on pregnancy-associated CT have been inconsistent, with some showing increased thickness^10–12 and others showing no difference from the values for nonpregnant controls^8,9. Our data suggest that such discrepancies may partly reflect gestational timing, as CT follows a nonlinear trajectory, increasing in mid-pregnancy and decreasing in late pregnancy.

The longitudinal pattern observed in this study can be interpreted in light of well-characterized, systemic physiological changes during pregnancy. From early to mid-pregnancy, the circulating plasma volume markedly increases, systemic vascular resistance decreases, and cardiac output increases^5,12 while estradiol-mediated nitric oxide production promotes peripheral vasodilation². These adaptations may enhance choroidal perfusion and could explain the transient thickening observed toward mid-gestation. Around 5–6 months, placental maturation and redistribution of maternal blood flow toward the uteroplacental circulation occur⁴, potentially reducing perfusion to nonessential vascular beds such as the choroid. In late pregnancy, plasma volume expansion plateaus⁴ while α-adrenergic receptor sensitivity and sympathetic tone increase²⁹, favoring vasoconstriction. These shifts correspond well with the progressive luminal thinning observed from 7 to 9 months. Given that the choroid is one of the most highly vascularized ocular tissues³⁰, such systemic circulatory adaptations are expected to induce structural changes. The relative stability of the stromal component, together with the predominant luminal alterations, supports the view that the observed choroidal dynamics primarily reflect vascular modulation consistent with pregnancy-related hemodynamic changes rather than stromal remodeling.

We also noted that the decrease in thickness was less pronounced around the seventh month. The mechanism remains unclear. Interestingly, this time frame coincides with an increased incidence of pregnancy-associated CSC, as reported in epidemiological studies⁷. While the overlap is noteworthy, our data do not establish a causal link, and further studies are required to clarify whether these phenomena are related.

This study has several limitations. First, the number of participants was very small. Increasing the sample size was difficult because healthy pregnant women without ocular symptoms rarely undergo ophthalmic imaging; moreover, acquisition of consent for repeated monthly examinations at a fixed time, which are necessary to reduce diurnal variations in CT, was challenging. Consequently, this study should be considered an exploratory investigation. Second, not all participants could be followed through delivery or the postpartum period, and early pregnancy data could not be obtained because of morning sickness. Third, because systemic hemodynamic and hormonal parameters were not collected in parallel, direct correlation analyses could not be performed. Despite these limitations, our study provides rare longitudinal data on choroidal changes during pregnancy, offering a reference for interpreting physiological versus pathological findings in pregnancy-related ocular conditions.

In conclusion, widefield SS-OCT demonstrated dynamic and regionally consistent changes in CT during pregnancy and the postpartum period. These alterations were primarily driven by luminal changes, while stromal thickness remained stable. Our findings provide new insights into pregnancy-associated ocular vascular adaptations and highlight the need for larger studies integrating systemic and fetal assessments. Such physiological benchmarks may help distinguish normal gestational changes from those observed in pregnancy-associated chorioretinopathies or abnormal pregnancies, thus providing a foundation for future studies aimed at clarifying disease-specific mechanisms.

Supplementary Information

Below is the link to the electronic supplementary material.

Author contributions

Conception and design of the study: TK, YM; data analysis and interpretation: TK, YM, NN, YA, YH; writing of the article: TK, YM; critical revision of the article: AT. All authors approved the final version of the manuscript.

Data availability

The datasets generated and/or analyzed in the current study are available from the corresponding author upon reasonable request.

Declarations

Competing interests

None of the authors have proprietary interests in any product described in this article. None of the authors have any conflicts of interest or proprietary interests in any product described in this article. The authors report the following relationships: T. Kogo: Canon; Y. Muraoka: Alcon Japan, Novartis Pharma, Bayer Yakuhin, Senju Pharmaceutical, Canon, Santen Pharmaceutical, AMO Japan, HOYA, Johnson & Johnson K.K.; N. Nishigori: None; Y. Akiyama: None; Y. Hama; None: A. Tsujikawa: Canon, Findex, Santen Pharmaceutical, Sumitomo Pharma, Astellas, Otsuka Pharmaceutical, Senju Pharmaceutical, Alcon Japan, Wakamoto Pharmaceutical, Chugai Pharmaceutical, HOYA, ROHTO NITTEN, Novartis Pharma, Bayer Yakuhin, AMO Japan, Kowa Company, MSD, Kowa Pharmaceutical, Johnson & Johnson K.K., ROHTO Pharmaceutical, Boehringer Ingelheim, Janssen Pharmaceutical, KYOWA KIRIN.